Recruitment Target Research Articles

Feasibility, acceptability, and preliminary efficacy of a self-directed online psychosocial intervention for women with metastatic breast cancer: Finding My Way-Advanced

PurposeFew digital interventions target patients with advanced cancer. Hence, we feasibility-tested Finding My Way-Advanced (FMW-A), a self-guided program for women with metastatic breast cancer.MethodsA single-site randomised controlled pilot trial was conducted. Participants were recruited through clinicians, professional networks, and social media and randomised to intervention or usual-care control. Participants were randomly allocated to either the intervention (FMW-A; a 6-week, 6-module CBT-based online self-directed psychosocial program for women with MBC + usual care resources) or control (usual care resources: BCNA’s Hope and Hurdles kit). Feasibility outcomes included rates of recruitment, uptake, engagement, and attrition. Distress, QOL, and unmet needs were evaluated for signals of efficacy, and qualitative feedback was collected to assess acceptability.ResultsDue to COVID-19 and funding constraints, the target recruitment of 40 was not reached (n = 60 approached; n = 55 eligible; n = 35 consented). Uptake was high (n = 35/55; 63.6%), engagement modest (median 3/6 modules per user), and attrition acceptable (66% completed post-treatment). Efficacy signals were mixed: compared to controls, FMW-A participants experienced small improvements in fear of progression (d = 0.21) and global QOL (d = 0.22) and demonstrated a trend towards improvements in cancer-specific distress (d = 0.13) and role functioning (d = 0.18). However, FMW-A participants experienced small-to-moderate deteriorations in general distress (d = 0.23), mental QOL (d = 0.51), and social functioning (d = 0.27), whereas controls improved. Qualitatively, participants (n = 4) were satisfied with the program, perceived it as appropriate, but noted some sections could evoke transient distress.ConclusionThe study demonstrated feasibility (high uptake and acceptable retention) and generated realistic recruitment estimates. While FMW-A appears promising for targeting cancer-specific distress and fear of progression, the mixed findings in quality of life and general distress warrant further revisions and testing.

The Black and African American Connections to Parkinson’s Disease (BLAAC PD) study protocol

Determining the genetic contributions to Parkinson’s disease (PD) across diverse ancestries is a high priority as this work can guide therapeutic development in a global setting. The genetics of PD spans the etiological risk spectrum, from rare, highly deleterious variants linked to monogenic forms with Mendelian patterns of inheritance, to common variation involved in sporadic disease. A major limitation in PD genomics research is lack of racial and ethnic diversity. Enrollment disparities have detrimental consequences on the generalizability of results and exacerbate existing inequities in care. The Black and African American Connections to Parkinson’s Disease (BLAAC PD) study is part of the Global Parkinson’s Genetics Program, supported by the Aligning Science Across Parkinson’s initiative. The goal of the study is to investigate the genetic architecture underlying PD risk and progression in the Black and/or African American populations. This cross-sectional multicenter study in the United States has a recruitment target of up to 2,000 individuals with PD and up to 2,000 controls, all of Black and/or African American ancestry. The study design incorporates several strategies to reduce barriers to research participation. The multifaceted recruitment strategy aims to involve individuals with and without PD in various settings, emphasizing community outreach and engagement. The BLAAC PD study is an important first step toward informing understanding of the genetics of PD in a more diverse population.

Biochemical plasticity of the Escherichia coli CRISPR Cascade revealed by in vitro reconstitution of Cascade activities from purified Cas proteins.

The most abundant clustered regularly interspaced short palindromic repeats (CRISPR) type I systems employ a multisubunit RNA-protein effector complex (Cascade), with varying protein composition and activity. The Escherichia coli Cascade complex consists of 11 protein subunits and functions as an effector through CRISPR RNA (crRNA) binding, protospacer adjacent motif (PAM)-specific double-stranded DNA targeting, R-loop formation, and Cas3 helicase-nuclease recruitment for target DNA cleavage. Here, we present a biochemical reconstruction of the E. coli Cascade from purified Cas proteins and analyze its activities including crRNA binding, dsDNA targeting, R-loop formation, and Cas3 recruitment. Affinity purification of 6His-tagged Cas7 coexpressed with untagged Cas5 revealed the physical association of these proteins, thus producing the Cas5-Cas7 subcomplex that was able to bind specifically to type I-E crRNA with an efficiency comparable to that of the complete Cascade. The crRNA-loaded Cas5-7 was found to bind specifically to the target dsDNA in a PAM-independent manner, albeit with a lower affinity than the complete Cascade, with both spacer sequence complementarity and repeat handles contributing to the DNA targeting specificity. The crRNA-loaded Cas5-7 targeted the complementary dsDNA with detectable formation of R-loops, which was stimulated by the addition of Cas8 and/or Cas11 acting synergistically. Cascade activity reconstitution using purified Cas5-7 and other Cas proteins showed that Cas8 was essential for specific PAM recognition, whereas the addition of Cas11 was required for Cas3 recruitment and target DNA nicking. Thus, although the core Cas5-7 subcomplex is sufficient for specific crRNA binding and basal DNA targeting, both Cas8 and Cas11 make unique contributions to efficient target recognition and cleavage.

Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial.

Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors may be more effective than GLP-1 receptor agonism alone in reducing body weight, but the cardiovascular (CV) effects are unknown. The authors describe the rationale and design of SYNCHRONIZE-CVOT, a phase 3, randomized, double-blind, parallel-group, event-driven, CV safety study of survodutide, a dual glucagon and GLP-1 receptor agonist, administered subcutaneously once weekly compared with placebo in adults with a body mass index≥27kg/m2 and established CV disease or chronic kidney disease, and/or at least 2 weight-related complications or risk factors for CV disease. The primary endpoint of SYNCHRONIZE-CVOT is time to first occurrence of the composite adjudicated endpoint of 5-point major adverse CV events. This global CV outcomes trial is currently enrolling, with a target recruitment of 4,935 participants. SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk. (A Study to TesttheEffect of Survodutide [BI 456906] on Cardiovascular Safety in People With Overweight or Obesity [SYNCHRONIZE-CVOT]; NCT06077864).

Trends in Government-Initiated Public Engagement in Canadian Health Policy From 2000 to 2021.

Canada has a rich history of public engagement in health policy; however, shifts in engagement practices over time have not been critically examined. We searched for cases of government-initiated public engagement in Canadian health policy from 2000 to 2021 at the federal, provincial (Ontario, British Columbia, Nova Scotia) and pan-Canadian levels. Government databases, portals and platforms for engagement were searched, followed by academic and grey literature using relevant search terms. A coding scheme was iteratively developed to categorize cases by target population, recruitment method and type of engagement. We identified 132 cases of government-initiated public engagement. We found a predominance of feedback and consultation engagement types and self-selection recruitment, especially at the federal level from 2016 onward. Engagements that targeted multiple populations (patients, public and other stakeholders) were favoured overall and over time. Just over 10% of cases in our survey mentioned efforts to engage with equity-deserving groups. Overall, our results identify a heavy reliance over time on more passive, indirect engagement approaches, which limit opportunities for collaborative problem solving and fail to include equity-deserving populations. Those overseeing the design and implementation of government-initiated public engagement will draw valuable lessons from this review to inform the design of engagement initatives.

Using publicly available UK datasets to identify recruitment sites to maximise inclusion of under-served groups: three case studies

Background There is strong evidence that those recruited into studies are not always representative of the population for whom the research is most relevant. Development of the study design and funding decisions are points in the research process where considerations about inclusion of under-served populations may usefully be made. Current practical guidance focuses on designing and modifying participant recruitment and retention approaches but an area that has not been addressed is recruitment site selection. Methods We present case studies of three NIHR funded trials to demonstrate how publicly available UK population datasets can be used to facilitate the identification of under-served communities for inclusion in trials. The trials have different designs, address different needs and demonstrate recruitment planning across Trauma centres, NHS Trusts and special educational settings. We describe our use of national freely available datasets, such as those provided by NHS Digital and the Office for National Statistics, to identify potential recruitment sites with consideration of health status, socio-economic status and ethnicity as well as clinical and risk factors to support inclusivity. For all three studies, we produced lists of potential recruitment sites in excess of the number anticipated as necessary to meet the recruitment targets. Discussion We reflect on the challenges to our approach and some potential future developments. The datasets used are all free to use but each has their limitations. Agreeing search parameters, acceptable proxies and identifying the appropriate datasets, then cross referencing between datasets takes considerable time and particular expertise. The case studies are trials, but the methods are generalisable for various other study types. Conclusion Through these exemplars, we aim to build on the NIHR INCLUDE project, by providing trialists with a much needed practical approach to embedding EDI into trial design at the grant application stage.

Validity of a Smartphone App to Objectively Monitor Performance Outcomes in Degenerative Cervical Myelopathy: Preliminary Findings From a Longitudinal Observational Study

Background Developing new clinical measures for degenerative cervical myelopathy (DCM) is an AO Spine RECODE-DCM research priority. Difficulties detecting DCM, and changes in DCM, cause diagnostic and treatment delays in clinical settings and heightened costs in clinical trials due to elevated recruitment targets. Digital outcome measures can tackle these challenges due to their ability to measure disease remotely, repeatedly, and more economically. Objective The study aims to assess the validity of MoveMed, a battery of performance outcome measures performed using a smartphone app, in the measurement of DCM. Methods A prospective observational study in decentralized secondary care was performed in England, United Kingdom. Validity and risk of bias were assessed using criteria from the COSMIN (Consensus-Based Standards for the Selection of Health Measurement Instruments) manual. Each MoveMed outcome was compared with 2 patient-reported comparators, with a priori hypotheses of convergence or divergence tested against consensus thresholds. The primary outcome was the correlation coefficient between the MoveMed outcome and the patient-reported comparators. The secondary outcome was the percentage of correlations that aligned with the a priori hypotheses. The comparators used were the patient-derived modified Japanese Orthopaedic Association score and the World Health Organization Quality of Life Brief Version questionnaire. Thresholds for convergence or divergence were set at ≥0.3 for convergence, <0.3 for divergence, and >0/<0 for directionality. Results A total of 27 adults aged 60 (SD 11) years who live with DCM and possess an approved smartphone were included in a preliminary analysis. As expected, MoveMed tests of neuromuscular function correlated most with questionnaires of neuromuscular function (≥0.3) and least with questionnaires of quality of life (<0.3). Furthermore, directly related constructs correlated positively to each other (>0), while inversely related constructs correlated negatively (<0). Overall, 74% (67/90) and 47% (8/17) of correlations (unidimensional and multidimensional, respectively) were in accordance with hypotheses. No risk-of-bias factors from the COSMIN Risk of Bias checklist were recorded. Overall, this was equivalent to “very good” quality evidence of sufficient construct validity in DCM. Conclusions MoveMed outcomes and patient-reported questionnaires converge and diverge in accordance with expectations. These findings support the validity of the MoveMed tests in an adult population living with DCM. Criteria from COSMIN provide “very good” quality evidence to support this.

An out-of-court community-based programme to improve the health and well-being of young adult offenders: the Gateway RCT.

Young adults represent a third of the United Kingdom prison population and are at risk of poor health outcomes, including drug and alcohol misuse, self-harm and suicide. Court diversion interventions aim to reduce the negative consequences of criminal sanctions and address the root causes of offending. However, evidence of their effectiveness has not yet been established. The Gateway programme, issued as a conditional caution, aimed to improve the life chances of young adults committing low-level offences. Participants agreed not to reoffend during the 16-week caution and, following a needs assessment, received individual support from a Gateway navigator and attended two workshops encouraging analysis of own behaviour and its consequences. To evaluate the effectiveness and cost-effectiveness of Gateway in relation to health and well-being of participants compared to usual process (court summons or a different conditional caution). Pragmatic, multisite, parallel-group, superiority randomised controlled trial with two 6-month internal pilots and a target sample size of 334. Randomisation between Gateway and usual process was on a 1 : 1 basis. Four Hampshire Constabulary sites recruited 18- to 24-year-old residents of Hampshire and Isle of Wight who were questioned for an eligible low-level offence. Semistructured interviews were also held with a sample of Gateway programme participants, staff and police study recruiters. Primary outcome was the Warwick-Edinburgh Mental Wellbeing Scale score at 12 months. Secondary outcomes included health status, alcohol and drug use, recidivism and resource use. Recruitment commenced in October 2019 and the trial stopped in April 2021. A total of 191 participants were recruited, with 109 randomised to Gateway and 82 to usual process. Due to an initial overestimation of potentially eligible young people and low retention rates, recruitment targets were adjusted, and a range of mitigating measures introduced. Although recruitment broadly met study progression criteria [35/50 (70%) Pilot 1: 64/74 (86%) Pilot 2], retention was low throughout (overall: data collected at week 4 was 50%: at week 16 it was 50%: 1-year 37%). Low retention was multifactorial, with one of the main barriers being difficulties contacting participants. It was therefore not possible to complete the randomised controlled trial or the health economics analyses. Qualitative interviews held with 58 individuals yielded rare insights into the benefits and limitations of this type of intervention, as well as barriers and facilitators in relation to recruitment in this setting. Despite close collaboration with the police to address recruitment and consent issues, expansion of the inclusion criteria and recruitment area and introducing other measures, the researchers were unable to collect sufficient data within an acceptable timeframe. The Gateway study was a unique endeavour to gather evidence for a potentially life-changing intervention for an underserved population. The experience gained indicates that randomised controlled trials of interventions, with a health-related outcome, are possible in this setting but point towards the need for conservative recruitment and retention estimates in this target population. Other study designs should be considered. The qualitative evaluation provided a range of valuable lessons for those seeking to design similar interventions or conduct research in similar settings. This study is registered as ISRCTN11888938. This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 16/122/20) and is published in full in Public Health Research; Vol. 12, No. 7. See the NIHR Funding and Awards website for further award information.

SIGNET: protocol for a multicentre, single-blind prospective, group sequential, randomised controlled trial to evaluate the benefits of a single dose of simvastatin given to potential organ donors declared dead by neurological criteria on outcomes in organ recipients

IntroductionSuccessful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased...

Care coordinator delivered method of levels therapy to improve engagement and other outcomes in early psychosis (CAMEO): protocol for a feasibility cluster-randomised controlled trial

BackgroundRates of disengagement from early intervention in psychosis (EIP) services are high. Care coordinators make up the largest staff group in EIP services and have the most frequent and sustained contact with service users. The quality of relationships between service users and care coordinators plays a central role in determining the effectiveness of EIP services. Care coordinators, however, are not routinely offered training in psychosocial interventions that could enhance the therapeutic impact of their role. Method of levels (MOL) is a flexible, transdiagnostic cognitive therapy with potential advantages over previously evaluated approaches. Training care coordinators in MOL could make their routine contacts with service users more helpful and improve outcomes such as recovery rates and levels of engagement.AimsThis study aims to assess the feasibility of training care coordinators in EIP services to deliver MOL, to understand whether this approach might improve service user engagement and recovery from psychosis compared to treatment as usual, and to assess the feasibility of conducting a cluster-randomised controlled trial (C-RCT) with clustering at the level of teams. Specific feasibility outcomes relate to the recruitment and retention of participants, care coordinators’ level of engagement with the MOL training and supervision programme, implementation of MOL in practice, and the acceptability of the intervention amongst participants.MethodsA feasibility parallel group cluster-randomised controlled trial (C-RCT) designs with two arms: (1) treatment as usual (TAU) or (2) TAU plus support from a care coordinator who has received training in MOL. Randomisation will take place at the level of EIP teams with an allocation ratio of 1:2 in favour of the intervention arm. Our recruitment target is 12 EIP teams, 24 care coordinators working in participating EIP teams, and up to 96 service users working with participating care coordinators. Outcomes will be collected at baseline, 3 months, and 6 months. Qualitative methods will be used to understand participants’ experiences of the study, MOL training programme, and MOL intervention.DiscussionThis is the first study that aims to evaluate the feasibility of training EIP care coordinators to deliver MOL in their routine practice. Training care coordinators in MOL could enhance the quality of relationships between care coordinators and service users and improve outcomes for people experiencing early psychosis. Results will be used to determine the appropriateness of progressing to a larger evaluation trial.Trial registrationThis study was prospectively registered with the ISRCTN Registry (14082421).

Utilizing technology for diet and exercise change in complex chronic conditions across diverse environments (U-DECIDE): feasibility randomised controlled trial

BackgroundDiet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service.MethodsU-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes.ResultsOf 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41–58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent.ConclusionsDigital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option.Trial registrationAustralia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Protocol for the Australian Type 1 Diabetes National Screening Pilot: Assessing the feasibility and acceptability of three general population screening models in children.

One third of Australian children diagnosed with type 1 diabetes present with life-threatening diabetic ketoacidosis (DKA) at diagnosis. Screening for early-stage, presymptomatic type 1 diabetes, with ongoing follow-up, can substantially reduce this risk (<5% risk). Several screening models are being trialled internationally, without consensus on the optimal approach. This pilot study aims to assess three models for a routine, population-wide screening programme in Australia. An implementation science-guided pilot study to evaluate the feasibility, acceptability and costs of three screening models in children will be conducted between July 2022 and June 2024. These models are as follows: (1) Genetic risk-stratified screening using newborn heel prick dried bloodspots, followed by autoantibody testing from 11 months of age; (2) genetic risk-stratified screening of infant (6-12 months) saliva followed by autoantibody testing from 10 months of age; and (3) autoantibody screening using capillary dried bloodspots collected from children aged 2, 6 or 10 years. Cohorts for each model will be recruited from targeted geographic areas across Australia involving ≥2 states per cohort, with a recruitment target of up to 3000 children per cohort (total up to 9000 children). The primary outcome is screening uptake for each cohort. Secondary outcomes include programme feasibility, costs, parental anxiety, risk perception, satisfaction, well-being and quality of life, and health professional attitudes and satisfaction. This pilot is the first direct comparison of three screening implementation models for general population screening. Findings will provide evidence to inform a potential national screening programme for Australian children. ACTRN12622000381785.

Stronger together: Implementing patient-reported symptom tool in routine cancer care in diverse Asia—A multi-national pilot feasibility study (PROMiSE-Pilot).

TPS180 Background: Patients diagnosed with cancer often experience disease or treatment-related symptoms, which can be under-elicited and under-appreciated by clinicians during time-poor consultations. This is particularly challenging in Asia where structural disparities in healthcare access mean oncology services are often under-resourced. Five oncologists from Thailand, India, Singapore, Philippines and Australia formed a working group as part of ASCO Asia-Pacific Leadership Development Program (LDP-AP). Systematic symptom monitoring using patient-reported outcomes measures (PROM) was identified as a potential solution to improve care in diverse Asian settings. PROM has demonstrated improved outcomes in Western settings but its utility in resource limited Asian contexts is less well established. A study was developed to evaluate the feasibility of implementing PROM in routine outpatient care across diverse cultural contexts in Asia. Methods: PROMiSE-Pilot is a prospective, multi-centre, feasibility study of integrating PROM in routine outpatient care across Asia. The Edmonton Symptom Assessment Scale questionnaire (ESAS-r) was selected as the PROM tool. Clinicians in 4 hospitals in Singapore, Manila, Bangkok and Hyderabad will be invited to participate, and their patients will be invited to complete the ESAS-r on paper before each visit. The primary aim is to evaluate if proportion of patients who complete ≥5 of 10 items on ESAS-r is ≥85% (Clopper Pearson). Secondary aims include assessing proportion who complete ≥8 and all 10 items and perceived utility of ESAS-r evaluated through surveys adapted to measure patient and clinician satisfaction. Site-specific patient, clinician, administrative barriers and facilitators will be studied. A pragmatic approach to context-specific implementation was adopted with each site developing its own process map for delivering the pilot and adapting to local patient demographics (e.g. low literacy), cultural contexts and resources. Translated versions of ESAS-r were acquired where necessary. Recruitment commenced in March 2024 following ethics approval at 2 sites. 87 patient encounters have been captured from 5 participating clinicians in Singapore. 5 clinicians have agreed to participate in Bangkok. Target recruitment is 200 encounters per site. Multi-centre data will be presented at the Breakthrough congress. Clinicians from ASCO LDP-AP identified PROM as a low-cost but potentially high-value approach to improving quality of care in resource limited settings in Asia. Understanding the feasibility of such a tool is vital prior to consideration of wider scale adoption by stakeholders. This co-developed multi-national pilot additionally demonstrates the value of collaboration, our strength in diversity and a pragmatic model for investigator-initiated studies in Asia.

Replicability, adaptability and long-term impact of the 'Healthy Youngsters, Healthy Dads' program in Newcastle, Australia.

'Healthy Youngsters, Healthy Dads' (HYHD) targets fathers to improve the health of their preschool-aged children. In a previous randomized trial, fathers and children experienced meaningful improvements in physical activity and eating behaviours. The next phase is to test the replicability and adaptability of HYHD when delivered in the community by trained facilitators. Fathers/father-figures and children aged 3-5 years were recruited from Newcastle, Australia into a 9-week, non-randomized trial with assessments at baseline, 10 weeks, and 12 months. The primary outcome was achievement of pre-registered targets for recruitment (≥ 96 dyads), attendance (≥ 70%), compliance (completing ≥ 70% of home-based tasks), fidelity (≥ 80% of content delivered as intended) and program satisfaction (≥ 4/5). Secondary outcomes included physical activity, nutrition, screen time and parenting measures. Process targets were surpassed for recruitment (140 fathers, 141 children), attendance (79% for fathers-only workshops, 81% for father-child sessions), compliance (80% of home-tasks completed), fidelity (99% for education, ≥ 97% for practical) and program satisfaction (4.8/5). Mixed effects regression models revealed significant effects in fathers for moderate-to-vigorous physical activity, co-physical activity, dietary intake and parenting practises, which were maintained at 12 months. Significant effects were also established for screen time at 10 weeks only. For children, significant effects were observed for screen time and dietary intake at 10 weeks, while effects on energy-dense, nutrient-poor foods and healthy, nutrient-dense core food intake were maintained at 12 months. Findings demonstrate the replicability and adaptability of HYHD when delivered in the community by local trained facilitators. Further investigation into how to optimally scale-up HYHD is warranted.

Inflammation and Macrophage Loss Mark Increased Susceptibility in a Genetic Model of Acute Viral Infection-Induced Tissue Damage.

M.R2k/b mice are identical to the MA/My parent strain aside from a 5.58-Mb C57L-derived region on chromosome 17 (Cmv5s) that causes increased susceptibility to acute murine CMV (MCMV) infection and the development of significant spleen tissue damage. Spleen pathology begins at the marginal zone (MZ), apparent by 2 d postinfection (dpi), and progresses throughout the red pulp by 4 dpi. To better understand how M.R2k/b mice respond to infection and how Cmv5s contributes to tissue damage in the spleen, we assessed the regulation of myeloid cells and inflammation during acute MCMV infection in MA/My and M.R2k/b mice. We found that Cmv5s drove increased neutrophil accumulation and cell death at the MZ, which corresponded with evidence of localized oxidative stress and increased overall spleen IL-6 and TGF-β1 early during infection. Further assessment of MCMV infection dynamics at the early MZ revealed infected SIGNR1+ MZ macrophages as the first apparent cell type lost during infection in these mice and the likely target of early neutrophil recruitment. Spleen macrophages were also identified as the mediators of differential spleen IL-6 and TGF-β1 between MA/My and M.R2k/b mice. Interrogation of MCMV progression past 2 dpi revealed substantial M.R2k/b F480+ red pulp macrophage loss along with buildup of oxidative stress and MZ macrophage debris that was not neutrophil dependent. Together we identify Cmv5s-driven macrophage loss and inflammation during acute MCMV infection corresponding with the spatial and temporal development of spleen tissue damage.

What works in implementing shared medical appointments for patients with diabetes in primary care to enhance reach: a qualitative comparative analysis from the Invested in Diabetes study

BackgroundDiabetes is a serious public health problem affecting 37.3 million Americans. Diabetes shared medical appointments (SMAs) are an effective strategy for providing diabetes self-management support and education in primary care. However, practices delivering SMAs experience implementation challenges. This analysis examined conditions associated with successful practice implementation of diabetes SMAs in the context of participation in a pragmatic trial.MethodsMixed methods study using qualitative and quantitative data collected from interviews, observations, surveys, and practice-reported data, guided by the practical, robust implementation and sustainability model (PRISM). Data were analyzed using qualitative comparative analysis (QCA). Successful implementation was defined as meeting patient recruitment targets (Reach) during the study period. Participants were clinicians and staff members from 22 primary care practices in Colorado and Missouri, USA.ResultsThe first necessary condition identified from the QCA was the presence of additional resources for patients with diabetes in the practice. Within practices that had these additional resources, we found that a sufficiency condition was the presence of an effective key person to make things happen with the SMAs. A second QCA was conducted to determine conditions underlying the presence of the effective key person (often performing functions of an implementation champion), which revealed factors including low or managed employee turnover, a strong baseline practice culture, and previous experience delivering SMAs.ConclusionsIdentification of key factors necessary and sufficient for implementation of new care processes is important to enhance patient access to evidence-based interventions. This study suggests that practice features and resources have important implications for implementation of diabetes SMAs. There may be opportunities to support practices with SMA implementation by enabling the presence of skilled implementation champions.Trial registrationRegistered at clinicaltrials.gov under trial ID NCT03590041, registered on July 18, 2018.

Evaluating a model of best practice in primary care led post-diagnostic dementia care: feasibility and acceptability findings from the PriDem study

ObjectivesTo evaluate the feasibility and acceptability of a primary care-based intervention for improving post-diagnostic dementia care and support (PriDem), and implementation study procedures.DesignA non-randomised, mixed methods, feasibility study.SettingSeven general practices...

P-746 Recruitment in randomised controlled trials: a conundrum

Abstract Study question What factors are associated with recruitment failure within the pre-planned study period? Summary answer Trials with a no-treatment arm, over four inclusion criteria, without a previous pilot and with low funding, are more likely to experience recruitment failure. What is known already Randomised controlled trials are considered to be the best strategy in evaluating the effectiveness of medical interventions, but they are often hampered by failure to recruit enough patients with the pre-planned study period. This represents a form of research waste. Little is known on variables related to recruitment failure within the pre-planned study period. Study design, size, duration This study was designed as a nationwide cohort study and included 71 randomized controlled trials supported by the Dutch Consortium for Women’s Health Research. We included trials initiated between March 1st 2003 and March 1st 2022. We extracted study data and information on predefined barriers and facilitators. Participants/materials, setting, methods Primary outcome was recruitment target not achieved within 6 months after the pre-planned recruitment period. Secondary outcomes included recruitment target not achieved within an extension of at least 12 months and premature termination of the trial. We used logistic regression to evaluate the association between potential indicators of recruitment failure and expressed these as odds ratios (OR) with corresponding 95% confidence intervals (CI). Main results and the role of chance Of the 71 trials included in our cohort, recruitment was not achieved within the pre-planned study period with a maximal extension period of 6 months or 12 months in 38 (54%) and 33 trials (46%), respectively. Indicators associated with higher chances on recruitment failure were a no treatment arm (OR 8.53 (95% CI 1.01 to 72.36)), a compensation fee of less than 200 euros per included patient (OR 3.16 (95% CI 1.18 to 8.45)) and a funding of less than 350.000 euros (OR 4.30 (95% CI 1.56 to 11.64)). Indicators associated with lower chances on recruitment failure were less than 4 inclusion criteria (OR 0.31 (95% CI 0.10 to 0.97)) and a preceding pilot study (OR 0.53 (95% CI 0.15 to 1.85)). Limitations, reasons for caution If we could have accessed an even larger cohort of studies we might have been able to identify more potential indicators for recruitment failure. Wider implications of the findings Investigators and grantproviders should consider our findings before the start of their studies, to optimize recruitmentcircumstances. If a trial is destined to have a suspected long recruitment, it seems wise to consider the relevance and urgency of the research question, and then accept a longer recruitment period with its consequences. Trial registration number not applicable

Результаты целевого трудоустройства медицинских работников в городах и сельской местности.

Targeted training of future medical workers and their guaranteed employment is one of the state measures to address the issue of the shortage of specialists. The key mission of targeted training is the balanced regulation by the organization of training and employment. Currently, there are not enough scientific studies on the results and effectiveness of this measure in the health care system, but many researchers emphasize the problems of targeted employment of medical workers. According to the studies of a number of authors, the imperfection of normative legal regulation of issues of targeted training allows graduates not to fulfill the obligations of employment in medical organizations upon graduation [3–9]. The purpose of the study. Conduct an analysis of indicators reflecting the specifics of targeted employment of health workers in organizations located in urban and rural areas in 2022 and 2023. Materials and methods. The study used statistical data for 85 constituent entities of the Russian Federation on the basis of an operative documented request to the health protection authorities of the constituent entities of the Russian Federation, containing information on the number of employed doctors and nursing staff within the framework of targeted training, as well as the planned values of targeted employment in accordance with the concluded contracts. The study period is 2022 and 2023. The total data on targeted employment of medical workers after completion of the specialty program and completion of residency in the context of the names of positions of doctors and nursing staff were analyzed. Analytical and descriptive statistics methods were used in the research process. Results. The share of doctors and nursing staff employed after completion of targeted training from the total number of medical workers in organizations located in rural areas is higher than the share of those recruited to work in urban medical organizations. On average, 1.3% of doctors and 0.21% of nursing staff are annually recruited to urban medical organizations as part of targeted employment out of the total number of the respective key medical personnel as of the end of the reporting year. In rural areas, these figures are 2.6% and 0.30%, respectively. Specialists are predominantly employed in urban medical organizations, while in rural areas – district doctors. The study revealed that in 2023 there were 128.1 target recruitments per 10,000 doctors in urban areas in a given year, and in 2022–124.8, i. e. the intensity of employment by target recruitment in urban areas increased by 2.6% in two years. In rural areas, there were 260.2 target recruitment admissions per 10,000 physicians in 2023 and 262.8 in 2022, that is, the intensity of target recruitment employment of physicians in rural areas decreased by 1% in two years. When analyzing the indicator comparatively, it is noted that in rural areas it is almost twice as high as in urban areas. Conclusions. Targeted employment of medical workers is an effective and efficient measure to attract medical personnel to organizations experiencing a shortage of them. The analysis has shown that the intensity rate of targeted employment per 10,000 physicians in urban areas of the country is lower than in rural areas, which amounted to 128.1 and 260.2, respectively. According to the results of the last two years, 60% of the doctors planned for targeted employment fulfilled their obligations, including 50% in rural areas. The main reason for the current level of employment is the failure to meet the planned indicators of targeted admission to training due to the violation of obligations by students and graduates, which requires the development of a special methodology for assessing the reasonable formation of the plan for targeted recruitment to educational organizations in the context of each medical organization. When comparing the number of vacant positions of doctors and the number of employed graduates within the framework of targeted recruitment, a significant range of the indicator among the subjects of the Russian Federation was revealed, which is presented in the interval from 1 to 29% (9.0±15.95). In this regard, it can be assumed that the number of persons employed under targeted recruitment does not depend on the additional demand for doctors and does not cover the existing deficit.

Pilot Randomized Controlled Trial of an Intervention to Promote HPV Uptake Among Young Women Who Attend Subsidized Clinics

ObjectiveTo evaluate the preliminary efficacy, acceptability, and feasibility of Step Up to Prevention, a technology-enhanced intervention to promote human papillomavirus (HPV) vaccination uptake among young minority and low-income women. DesignA pilot randomized controlled trial. SettingTwo federally supported outpatient clinics in a large city in the northeastern United States. ParticipantsWomen who were 18 to 26 years of age (N = 60). MethodsWe randomized participants into four groups: computer information, in-person tailored, combined, and usual care. We administered computer-assisted self-interview surveys before the intervention (baseline), immediately after the intervention (postintervention), and after their clinic visit (post–clinic visit). We conducted a descriptive analysis of participant characteristics. For preliminary efficacy, we used logistic regression–assessed HPV vaccine initiation uptake rates, and we used descriptive statistics to compare theoretical mediators. We used conventional content analysis to assess participant feedback about intervention acceptability. We assessed feasibility through recruitment and retention rates and our ability to deliver the intervention. ResultsWe observed significant differences in initial HPV vaccine uptake between the intervention groups and the usual care group. Participant feedback indicated that the intervention was acceptable, empowering, and informative. We met our recruitment target, maintained a high retention rate (98%), and delivered the complete intervention to all participants. ConclusionWe report the preliminary efficacy, acceptability, and feasibility of this intervention to promote HPV vaccine initiation among young women in federally subsided health care settings by advancing favorable views and improving knowledge about HPV vaccination.